The "closed-loop artificial pancreas," a device that would measure glucose level and deliver insulin automatically as needed, has been an elusive goal in the treatment of diabetes. There are three essential components: the blood glucose sensor, linking algorithms and the delivery system. For the first time, a viable sensor and a proven delivery system are now available for research. The broad goal of this clinical research proposal is to complete the studies needed to link the sensor to the delivery system, paving the way for a functional closed-loop artificial pancreas. First, we will make a detailed analysis of sensor signal as it reflects glucose level in normal and diabetic humans. Second, we will study the precise pharmacokinetics of insulin delivery by external and implantable insulin pumps. Third, analysis of these two data sets will provide the basis for algorithms that link the sensor signal to insulin delivery. A formal safety analysis will evaluate the safety features needed in a closed loop device. In the last year of the project, the entire system will be tested and fine-tuned. This project takes advantage of our relatively extensive investigational experience with mechanical insulin delivery pumps in people with diabetes, and the recent availability, for research, of a subcutaneously placed, glucose oxidase-based continuous glucose sensor. The investigators have established experienced with clinical research in diabetes, and the resources of an excellent General Clinical Research Center. The co-investigators have extensive experience with mathematical modeling of biologic systems. There is a close working relationship between the research team and the manufacturer of the sensor and pumps, as reflected by the Interactive Research Project Grant collaboration, and by a long-standing history of collaboration. It is essential to emphasize that we do not anticipate completion of a manufacturable, clinically usable, commercially viable artificial pancreas within the time-frame of this work. Rather, we aim to complete the basic studies and modeling analyses that would form the basis of such a system, and demonstrate the feasibility of linking the sensor to the delivery device. If these studies and these trials were successful, they would be a major step towards development of a clinically useful close-loop artificial pancreas.